Cytomegalovirus Infection and Guillain-Barré Syndrome: The First Case-Control Study in Iran

Objectives Guillain-Barré syndrome (GBS) is an immune-mediated disease of the peripheral nervous system affecting all age groups around the world. Although the pathogenesis and optimal treatment of GBS have not yet been completely identified, one of the most common infectious diseases to trigger the syndrome is cytomegalovirus (CMV) infection. The GBS following CMV infection is rarely reported in childhood, and there have been no data on GBS with antecedent CMV infection in children in Iran. The current study aimed to evaluate the association between CMV infection and GBS in children in Iran. Materials & Methods The case-control study design was used for 30 GBS cases and 30 matched controls. All the serum samples were tested for the presence of anti-CMV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies using a commercially available enzyme-linked immunosorbent assay (EUROIMMUN Medizinische, Germany). The CMV viral deoxyribonucleic acid (DNA) in the specimen was detected using polymerase chain reaction (PCR) (Cytomegalovirus PCR Detection Kit, CinnaGen Co., Iran). Results Anti-CMV IgG antibodies were detected in 97% of the GBS patients and 93% of the healthy controls. Anti-CMV IgM antibodies were demonstrated in 33% of the healthy controls (n=10) and 33% of the GBS children (n=10). The borderline level of anti-CMV IgM antibodies was observed in 23% of the healthy controls (n=7) and 13% of the GBS children (n=4) (P=0.57). None of the specimens from both controls and GBS cases was positive for CMV DNA using PCR. Conclusion The obtained data demonstrated the presence of anti-CMV antibodies in the majority of both GBS patients and controls. Moreover, no relation was observed between CMV infection and GBS. However, it is highly recommended to perform further studies with a large sample size.


Introduction
Guillain-Barré syndrome (GBS) is an immunemediated disease of the peripheral nervous system occurring after an infectious disease in 60-70% of cases (1,2). The GBS affects all age groups around the world; however, there has been a higher incidence in adults than that in children (3). The annual incidence of GBS in children is estimated at 0.34-1.34 cases per 100 000 individuals, with a slightly higher incidence in males (3,4).
Although the pathogenesis and optimal treatment of GBS have not yet been completely identified (3), it has been reported that more than 70% of GBS patients have a history of a viral infection approximately 6 weeks before the development of the disease (3). Moreover, the possible role of some medications or procedures as probable etiologies has been reported (5). Some of the pathogenic triggers of GBS include viruses, such as Epstein-Barr virus, cytomegalovirus (CMV), hepatitis, varicella (6-9), Campylobacter jejuni (10,11), and Mycoplasma pneumoniae (12).
More recently, Zika virus and severe acute respiratory syndrome coronavirus 2 infections have also been reported as the potential triggers of GBS (2,13,14). Campylobacter jejuni enteritis controls and GBS cases was positive for CMV DNA using PCR.

Conclusion
The obtained data demonstrated the presence of anti-CMV antibodies in the majority of both GBS patients and controls. Moreover, no relation was observed between CMV infection and GBS. However, it is highly recommended to perform further studies with a large sample size.
Keywords: Guillain-Barré syndrome; Cytomegalovirus; Children DOI: 10.22037/ijcn.v15i4.31285 (in 21-32% of cases) and primary CMV infection (in 10-22% of cases) have been reported as the most common infectious diseases to trigger the syndrome (7,15). It has been reported that the risk of developing GBS following CMV infection is close to 1 in 1000 (7). However, the role of CMV infection in the prognosis of GBS is also still unclear (3,8,9).
There has been limited evidence on the epidemiology and prognostic factors of GBS following primary infection with CMV and the roles of anti-ganglioside antibodies, cellular immune responses, and viral replication (7). The GBS following CMV infection is rarely reported in childhood (16), and there have been no data on

GBS with antecedent CMV infection in children in
Iran. Therefore, the current study aimed to evaluate the association between CMV infection and GBS in children in Iran.  (17). The precise diagnosis of GBS Hughes functional classification scores at three different time points were calculated using clinical information available in the medical records. The Hughes functional classification score ranges from 0-6 as grade 0 (healthy), grade 1 (minor symptoms or signs, able to run), grade 2 (able to walk without assistance but unable to run), grade 3 (able to walk with assistance), grade 4 (bed-or chair-bound), grade 5 (requiring assisted ventilation for at least part of the day), and grade 6 (dead) (18).  This study evaluated the association between CMV infection and GBS in 30 GBS children and 30 healthy age-and gender-matched controls. It was demonstrated that there was no association between preceding CMV infection and GBS development. Similar to a previous report, GBS was more common in males than females (19).

Materials & Methods
The incidence of GBS and its relation to seasonal variation was observed in the present study with predominance in the winter that is in contrast to the results of a previous study reporting months closely followed by spring (19).
In the current study, plasma CMV PCR test results were negative in all cases of both groups; however, The results of the current study showed that 29 patients (97%) with GBS were CMV-IgG seropositive among whom 10 patients were CMV-IgM negative seropositive, indicating that the 20 patients (67%) with GBS were not in the acute